累积铅暴露与认知障碍的 DNA 甲基化生物标志物

IF 7.7 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environmental Research Pub Date : 2024-11-06 DOI:10.1016/j.envres.2024.120304

Kanghong Shao , Yu Yu , Beate Ritz , Kimberly C. Paul , the Alzheimer's Disease Neuroimaging Initiative (ADNI)

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引用次数: 0

摘要

背景：最新证据表明，累积性低浓度铅暴露会对老年人的认知功能产生不利影响。迄今为止，测量骨铅暴露的少数研究依赖于 KXRF（K-X 射线荧光法），而这种方法在大型社区研究中大多无法使用。在此，我们在阿尔茨海默病神经影像学倡议（ADNI）队列中采用了一种基于甲基化的骨铅和血铅估算方法：方法：利用血液 DNA 甲基化 (DNAm) 生物标记物估算了 625 名 ADNI 队列参与者的胫骨、髌骨和血铅水平。认知功能采用蒙特利尔认知评估（MoCA）进行评估。采用线性混合效应回归模型进行纵向分析。参与者的基线年（2010-2014年）和随访年（2014-2015年）不同：在整个随访过程中，DNAm得出的胫骨和髌骨铅含量与MoCA得分呈负相关，而DNAm得出的血铅含量与MoCA得分无关。平均而言，我们观察到随着DNAm胫骨铅含量的增加，MoCA评分降低（每四分位数间距（IQR）：β=-0.23；95%CI：-0.44，-0.03），DNAm髌骨铅含量也降低，但后者较弱（每四分位数间距（IQR）：β=-0.19；95%CI：-0.41，0.04）。按性别分层时，随着 DNAm 胫骨导联的增加，女性认知功能的下降幅度（每 IQR β=-0.34；95%CI：-0.65，-0.04）大于男性（每 IQR β=-0.15；95%CI：-0.42，0.13）。具有一个或两个APOE4等位基因的参与者（每IQR β=-0.37；95%CI：-0.74，-0.01）的MoCA评分每增加一个DNAm胫骨导联IQR的估计下降幅度（每IQR β=-0.14；95%CI：-0.38，0.10）要比那些等位基因为零的人（每IQR β=-0.14；95%CI：-0.38，0.10）大：这些发现加强了长期累积铅暴露水平与老年人认知功能下降有关的证据，尤其是在女性和一个或两个 APOE4 等位基因携带者中。这些基于全血甲基化数据的研究结果证实了之前使用 KXRF 测量骨铅的流行病学研究。

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DNA methylation biomarkers for cumulative lead exposures and cognitive impairment

Background

Recent evidence suggests that cumulative low-level lead exposure has adverse effects on cognitive function in the elderly. To date, the few studies that have measured bone lead exposure relied on K-X-ray fluorescence (KXRF), methods that are mostly unavailable in large community-based studies. Here, we employ a methylation-based estimation method for bone and blood lead in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.

Methods

Tibia, patella, and blood lead levels were estimated using blood DNA methylation (DNAm) biomarkers in 625 participants from the ADNI cohort. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Longitudinal analyses were conducted using linear mixed-effect regression models. Participants had different years of baseline (2010–2014) and follow-up visits (2014–2015).

Results

DNAm derived tibia and patella lead levels were negatively associated with MoCA scores throughout follow-up, while DNAm derived blood lead level was not associated with MoCA scores. On average, we observed lower MoCA scores with increasing DNAm tibia lead (per interquartile range (IQR): β = −0.23; 95% CI: −0.44, −0.03) and DNAm patella lead, albeit the latter was weaker (per IQR: β = −0.19; 95% CI: −0.41, 0.04). When stratifying by gender, women showed a stronger decrease in cognitive function with increasing DNAm tibia lead (per IQR β = −0.34; 95% CI: −0.65, −0.04) than men (per IQR β = −0.15; 95% CI: −0.42, 0.13). The estimated decrease in MoCA scores per DNAm tibia lead IQR increase was stronger among participants with one or two APOE4 alleles (per IQR β = −0.37; 95% CI: −0.74, −0.01) than those with zero alleles (per IQR β = −0.14; 95% CI: −0.38, 0.10).

Conclusion

These findings strengthen the evidence that cumulative long-term lead exposure levels are associated with decreased cognitive function in the elderly, especially among women and carriers of one or two APOE4 alleles. These findings based on whole blood methylation data corroborate previous epidemiologic studies that used KXRF for measuring bone lead.

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来源期刊

Environmental Research 环境科学-公共卫生、环境卫生与职业卫生

CiteScore

12.60

自引率

8.40%

发文量

2480

审稿时长

4.7 months

期刊介绍： The Environmental Research journal presents a broad range of interdisciplinary research, focused on addressing worldwide environmental concerns and featuring innovative findings. Our publication strives to explore relevant anthropogenic issues across various environmental sectors, showcasing practical applications in real-life settings.